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New page: '''Unreleased structure''' The entry 5lit is ON HOLD Authors: Description: Category: Unreleased Structures
 
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'''Unreleased structure'''


The entry 5lit is ON HOLD
==Structure of the DNA duplex d(AAATTT)2 with the potential antiparasitic drug 6XV at 1.25 A resolution==
<StructureSection load='5lit' size='340' side='right'caption='[[5lit]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lit]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LIT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6XV:4-(imidazolidin-2-ylideneamino)-~{N}-[4-(imidazolidin-2-ylideneamino)phenyl]benzamide'>6XV</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5lit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lit OCA], [https://pdbe.org/5lit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lit RCSB], [https://www.ebi.ac.uk/pdbsum/5lit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lit ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of &gt;70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amin o)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-im idazol-2-yl)amino)benzamide] as potential drugs for HAT. Both compounds show in vitro effects against T. brucei and in vivo curative activity in a mouse model of HAT. The main objective was to identify their cellular target inside the parasite. We were able to demonstrate that the compounds have a clear effect on the S-phase of T. brucei cell cycle by inflicting specific damage on the kinetoplast. Surface plasmon resonance (SPR)-biosensor experiments show that the drug can displace HMG box-containing proteins essential for kDNA function from their kDNA binding sites. The crystal structure of the complex of the oligonucleotide d[AAATTT]2 with compound 1 solved at 1.25 A (PDB-ID: 5LIT) shows that the drug covers the minor groove of DNA, displaces bound water and interacts with neighbouring DNA molecules as a cross-linking agent. We conclude that 1 and 2 are powerful trypanocides that act directly on the kinetoplast, a structure unique to the order Kinetoplastida.


Authors:  
Functional and structural analysis of AT-specific minor groove binders that disrupt DNA-protein interactions and cause disintegration of the Trypanosoma brucei kinetoplast.,Millan CR, Acosta-Reyes FJ, Lagartera L, Ebiloma GU, Lemgruber L, Nue Martinez JJ, Saperas N, Dardonville C, de Koning HP, Campos JL Nucleic Acids Res. 2017 Jun 16. doi: 10.1093/nar/gkx521. PMID:28637278<ref>PMID:28637278</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 5lit" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Dardonville C]]
[[Category: Lourdes Campos J]]
[[Category: Millan CR]]
[[Category: Saperas N]]
[[Category: De Koning HP]]
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